Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women.

Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however, their frequency increases in aged patients. The present work demonstrates that NE breast carcinomas in elderly women can also express an apocrine immunophenotype and analyzes the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >/=50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and solid cohesive histotypes) coexpressed the apocrine marker. In these cases, specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3), including one case of atypical carcinoid, were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors in apocrine differentiation. We demonstrated that the level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. The most original result of our study is therefore the demonstration of a possible divergent apocrine differentiation of NE breast carcinomas that might be regulated by the activation of androgen receptors in elder patients. In addition, the possibility for using Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.     

Neues in der WHO-Klassifikation 2014 der Tumoren des Corpus uteri

The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma). Besides a papillary architecture serous carcinomas may show solid and glandular features and TP53 immunohistochemistry with an “all or null pattern” assists in the diagnosis of serous carcinoma with ambiguous features. Neuroendocrine neoplasms are categorized in a similar way to the gastrointestinal tract into well differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas (small cell and large cell types). Leiomyosarcomas of the uterus are typically high grade and characterized by marked nuclear atypia and lively mitotic activity. Low grade stromal neoplasms frequently show gene fusions, such as JAZF1/SUZ12. High grade endometrial stromal sarcoma is newly defined by cyclin D1 overexpression and the presence of the fusion gene YWHAE/FAM22 and must be distinguished from undifferentiated uterine sarcoma. Carcinosarcomas (malignant mixed Mullerian tumors MMMT) show biological and molecular similarities to high-grade carcinomas.     

Breast cancers with special genetic-phenotypic correlations

Some invasive breast carcinomas are unique in that they show a specific recurrent genetic abnormality that is associated with distinct morphologic features. These tumors are triple-negative and are generally associated with a favorable prognosis compared with other triple-negative breast carcinomas. Adenoid cystic carcinoma is a biphasic epithelial-myoepithelial invasive carcinoma that like its salivary gland counterpart, is characterized by a recurrent t(6; 9) (q22-23; p23-24) translocation which results in the formation of a MYB-NFIB fusion gene. Secretory carcinoma shows a recurrent (12; 15); (p13; q25) translocation that results in an ETV6-NTRK3 gene fusion, which is also seen in mammary analogue secretory carcinoma of the salivary gland. Tall cell carcinoma with reversed polarity, previously called “breast tumor resembling the tall cell variant of papillary thyroid carcinoma,” and “solid papillary carcinoma with reverse polarity” shows IDH2 hotspot mutations, which are rare in other breast carcinomas. This review will provide an overview of the morphologic, immunohistochemical, molecular, and clinical features of these rare examples of breast cancers with special genetic–phenotypic correlations.     

Expression of the neuroendocrine phenotype in carcinomas of the breast

Neuroendocrine (NE) features are detectable in carcinomas of the breast either as scattered cells immunoreactive for NE markers in carcinoma of the usual type (NOS), or as special type of tumors where the vast majority of the cells display NE characteristics. The former type of lesions, whose biological and diagnostic significance is not clear yet, might reproduce the same phenomenon known to occur in carcinomas of the gastrointestinal tract and pancreas. In the present review we focus on the latter type of lesions, a spectrum of breast tumors largely composed of NE cells. These carcinomas, that we consider the "NE differentiated carcinomas of the breast," are here distinguished from "breast carcinomas NOS with NE differentiation." The diagnostic and histogenetic features of the various types of "NE differentiated carcinomas of the breast," their histological and cytological features and the role and value of ancillary diagnostic techniques, are reviewed. Data of the literature are discussed and related to a relatively large personal series. In addition, divergent differentiation in NE carcinomas of the breast, which is a relatively frequent phenomenon of diagnostic interest but of unknown significance (mainly involving mucinous intra- and extracellular production) is discussed.     

Endometrioid carcinoma of the fallopian tube resembling a female adnexal tumor of probable wolffian origin

Endometrioid carcinoma of the fallopian tube resembling a female adnexal tumor of probable wolffian origin (FATWO) is a rare, recently delineated, low-grade carcinoma that may be confused with both FATWO and high-grade carcinoma. Only about 20 cases have been reported so far, but it probably represents almost half of the endometrioid carcinomas of the fallopian tube. It has a better prognosis than conventional tubal endometrioid and serous carcinomas. Macroscopically, the tumors form a small, solid, polypoid mass that is usually confined within the tube. Microscopically, the tumors are characterized by proliferations of spindle cells in whorls and closely packed confluent elongated glands with focal tubular, sieve-like, and papillary structures. Unlike FATWO, this variant of endometrioid carcinoma exhibits focal squamous differentiation, intraluminal mucin, mild to moderate nuclear atypia, and occasional mitosis. Unlike FATWO, tumor cells are negative for inhibin-alpha and calretinin.     

Papillary and neuroendocrine breast lesions: the WHO stance

In this review, we highlight adaptations in the WHO 2012 classification of papillary and neuroendocrine breast lesions as compared with the previous 2003 version. Consensus criteria for distinguishing atypical ductal hyperplasia from ductal carcinoma in situ within an intraductal papilloma are proposed. The absence of myoepithelial cells around the wall of an encapsulated papillary carcinoma, although raising consideration of an indolent tumour with minimal invasion, is currently regarded as in‐situ disease for staging purposes. The majority of solid papillary carcinomas are classified as in‐situ tumours, but lesions with irregular tumour islands within desmoplastic stroma may be considered to be invasive. The diagnosis of solid papillary carcinoma without further qualification as either in‐situ or invasive disease is discouraged. When invasive papillary carcinoma is seen in the breast, metastatic papillary carcinoma from other organ sites needs to be excluded. WHO 2012 classifies neuroendocrine breast tumours as well‐differentiated neuroendocrine tumour, small‐cell carcinoma, and invasive breast carcinoma with neuroendocrine differentiation. There is currently no clinical impact of identifying neuroendocrine differentiation in conventional invasive breast carcinomas, apart from acknowledging its frequent occurrence in subtypes such as the hypercellular variant of mucinous carcinoma and solid papillary carcinoma.     

Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges

Tang F, Wei B, Tian Z, Gilcrease M Z, Huo L, Albarracin C T, Resetkova E, Zhang H, Sahin A, Chen J, Bu H, Abraham S & Wu Y
(2011) Histopathology 59 , 106–115 Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges Aims: The aim of this study was to review the histomorphological features of primary neuroendocrine carcinomas (NEC) of the breast, in order to identify features useful in recognition of this entity for appropriate classification. Methods and results: 2003 World Health Organization (WHO) classification of tumors of the breast and female genital organs defined NEC of the breast as a subtype of invasive mammary carcinoma in which >50% of the tumor cells express neuroendocrine markers. Seventy‐four cases that fulfilled the WHO diagnostic criteria for NEC of the breast, excluding small cell carcinoma and low‐grade solid papillary carcinoma with a predominant in‐situ component, were identified between 1984 and 2008 from MD Anderson Cancer Center, and were included in the study. NECs of the breast had variable histomorphological features. The most common histologic patterns were papillary (80%) and nested (64%). Mixed growth patterns were common (59%), including admixed ductal component. The tumor cells could be polygonal, round, plasmacytoid, spindled, or with signet ring cell features. The cytoplasm could be granular, eosinophilic, clear, or finely vacuolated. These tumors frequently mimicked invasive or in situ ductal carcinoma, or invasive lobular carcinoma. Conclusions: NEC of the breast is underrecognized. Careful attention to cytologic and architectural features can help to identify cases that require further immunophenotypic confirmation for correct tumor classification.     

Immunophenotypic and genomic characterization of papillary carcinomas of the breast

Papillary carcinomas are a special histological type of breast cancer and have a relatively good outcome. We characterized the genomic and phenotypic characteristics of papillary carcinomas to determine whether they would constitute an entity distinct from grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs). The phenotype of 63 papillary carcinomas of the breast and grade- and ER-matched IDC-NSTs was determined by immunohistochemistry. DNA of sufficient quality was extracted from 49 microdissected papillary carcinomas and 49 microdissected grade- and ER-matched IDC-NSTs. These samples were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY sequencing analysis of 19 known oncogenes. Papillary carcinomas were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. Papillary carcinomas displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however, the patterns of gene copy number aberrations found in papillary carcinomas were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of papillary carcinomas and grade- and ER-matched IDC-NSTs, respectively. The genomic profiles of encapsulated, solid and invasive papillary carcinomas, the three morphological subtypes, were remarkably similar. Our results demonstrate that papillary carcinomas are a homogeneous special histological type of breast cancer. The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers, rather than as a distinct entity. Furthermore, the good prognosis of papillary carcinomas may stem from the low rates of lymph node metastasis and p53 expression, low number of gene copy number aberrations and high prevalence of PIK3CA mutations.     

Composite encapsulated papillary carcinoma and solid papillary carcinoma

Encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC) are distinctive variants of intraductal papillary carcinomas, each accounting for <1% of breast carcinomas. Here we report a composite carcinoma consisting of EPC and SPC. A 73‐year‐old woman was found to have a high density mass in the left breast on mammogram. A biopsy showed intermediate to high grade ductal carcinoma in situ (DCIS). Gross examination of the lumpectomy specimen revealed a solid, multinodular mass. Microscopic examination demonstrated two morphologically distinct intraductal carcinomas intermingled with each other. One had delicate papillae in multi‐cystic spaces surrounded by thick fibrous capsule, consistent with EPC. The other had solid tumor nests with delicate fibrovascular cores. The cells were monotonous with round nuclei and salt and pepper‐like chromatin, characteristic of SPC. The lack of myoepithelial cells within the papillae and at the periphery of the lesion was confirmed by immunostaining for p63 and CK5/6. Neuroendocrine differentiation of SPC was demonstrated by neuron specific enolase staining. To our knowledge, this is the first reported case of composite EPC and SPC. It raises an interesting question as to a possible common pathway of carcinogenesis of these two rare variants.     

Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases

A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine (NE) differentiation. This study presents a structural, immunologic, and electron microscopic analysis of 51 cases in order to establish positive criteria for identification of these tumors, their incidence, variants, and biological behavior. Argyrophilia (by the Grimelius procedure), presence of chromogranin A and/or B, and of synaptophysin are the most reliable histochemical features, correlating with the ultrastructural demonstration of dense-core secretory granules and of clear vesicles of the synaptic type. Structural features alone may be suggestive, but do not prove NE differentiation, which has to be established by additional techniques. Seven histologic types were identified, but those herein described as types A, B, and C, which show cohesive, mucoid, and mixed patterns, respectively, comprise the vast majority of the tumors. Rare NE carcinomas of the breast show structural similarities to Merkel cell and oat cell carcinomas, and behave as highly aggressive tumors. Type B (mucinous) tumors proved to be relatively indolent, while the most frequent types of endocrine tumors (types A and C) have an intermediate grade of malignancy. The analysis of a consecutive series of 100 cases of breast cancer indicates that about 8% of breast carcinomas display some degree of NE differentiation.     

Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.     

Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.     

Correlation between neovascularisation and neuroendocrine differentiation in prostatic carcinoma

Neuroendocrine (NE) differentiated tumor cells are found in almost all prostatic carcinomas. Prostatic carcinomas with a high NE differentiation have a poor prognosis and increased metastatic potential. A relationship between the neovascularisation density in the tumor and the metastatic potential in prostatic carcinoma is well known. NE cells and microvessels were demonstrated immunohistochemically on 102 radical prostatectomy specimens using antibodies against Chromogranin A and CD34. Standard areas (7.9 mm2) of maximal Chromogranin A expression and highest vascularisation were determined and topographically related by light microscopy. Area density of microvessels was evaluated morphometrically. NE tumor cells were present in all prostatic carcinomas studied. High grade prostatic carcinomas expressed significantly more NE tumor cells and exhibited a higher neovascularisation than low grade carcinomas. There was significantly higher neovascularisation in high grade tumors with many, as compared to high grade tumors with few, NE tumor cells. Poorer pathological staging correlated with increased neovascularisation and stronger NE differentiation. A topographical relationship between the area of maximal NE tumor cells and the area of highest neovascularisation was found in 80.4% of all cases. An analysis of variance revealed a large number of NE tumor cells as the only predictor of an increased neovascularisation (p = 0.0006). These observations support the concept that increased neovascularisation is influenced not only by poor pathological grading but also by a high NE differentiation.     

Controversial issues and new discoveries in lung neuroendocrine tumors

Lung neuroendocrine (NE) tumors consist of four histologic subtypes, which are usually classified based on a three-tiered prognostic scheme. They are typical carcinoid (TC) as low-grade malignant tumors, atypical carcinoid (AD) as intermediate-grade malignant tumors, and large cell NE carcinoma (LCNEC) and small cell lung carcinoma (SCLC), both of which are high-grade malignant tumors. This three-tiered classification is based solely on histologic grounds and is a source of controversy especially when dealing with borderline or “gray zone” categories (TC vs. AC, AC vs. LCNEC, LCNEC and SCLC). In this review, controversial issues regarding the histologic classification will be discussed, and an innovative grading system that incorporates Ki-67 labeling index will be described. In addition, the recently discovered molecular alterations involved in TC/AC, as well as pathways involved in high-grade NE carcinomas, will be discussed in order to elucidate the differences in pathogenesis and biology between carcinoid tumors and high-grade NE carcinomas.     

Keratin subsets in papillary and follicular thyroid lesions

 Previous studies indicate that keratins 7, 8 and 18 are present in all thyroid papillary and follicular lesions, but the distribution of other keratins has been incompletely characterized. The profile of individual keratin (K) polypeptides was evaluated immunohistochemically in over 200 non-neoplastic and neoplastic thyroid papillary and follicular lesions. Monoclonal antibodies to K19, K17, K16, K5/6 and K10 were applied in paraffin sections of formaldehyde-fixed tissue. K19 was present variably, often only focally in goitres, and was present only sporadically in papillary hyperplasia. However, K19 was strongly and uniformly expressed in virtually all papillary carcinomas, indicating differential diagnostic usefulness in differentiating papillary hyperplasia and papillary carcinoma. About half of the follicular carcinomas (defined as tumours strictly excluding the follicular variant of papillary carcinoma) were also strongly K19-positive, suggesting that K19 patterns are not reliable in differentiating papillary and follicular carcinoma. K17 and K5/6 were present in cysts and squamous metaplasia of goitres, and focally in papillary but only exceptionally in follicular carcinoma in areas of squamous differentiation and tumour cells in desmoplastic stroma. K16 in turn was present only focally in well-developed squamous metaplasia in goitres but was not found in differentiated thyroid carcinomas. K10, a high-molecular-weight keratin typical of epidermal differentiation, was identified neither in non-neoplastic nor in neoplastic differentiated thyroid lesions, including squamous metaplasia. These results indicate that papillary carcinomas differ from other differentiated thyroid tumours in their varying, usually focal, expression of stratified epithelial keratins that are partly but not exclusively related to squamous differentiation in such lesions. However, papillary carcinomas do not express truly epidermally restricted keratins; their previously described reactivity with polyclonal ”epidermal keratin” antibodies most probably results from the reactivity of such antibodies with K19. Received: 14 April 1997 / Accepted: 28 May 1997     

Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma

In a study of 1529 patients with primary operable breast carcinoma we have assessed the effect of applying both histological grade and tumour type to determine their comparative value as prognostic factors in human breast cancer. The prognostic group the patient was placed in, based on histological type alone, was less accurate than using grade and type together for many tumours. The importance of performing histological grading of ductal/no special type carcinoma (50% of the women in this series) is confirmed in this series. The 10-year-survival varied from 76% for women with grade 1 carcinoma to 39% for those with grade 3 tumours. Some of the 'special types' of breast carcinoma including tubular, tubulo-lobular, invasive cribriform and grade 1 mucinous carcinomas behaved as would be predicted, with a greater than 80% 10-year-survival in this series. Others, including grade 2 mucinous carcinomas, however, behaved less well with a 60% to 80% 10-year-survival. Indeed, many of the histological tumour types including tubular mixed, ductal/no special type, mixed ductal with special type and lobular carcinomas of classical, solid or mixed types showed a variation in behaviour that could not be predicted by typing alone. Histological grade and tumour type, when used together, more accurately predicted prognosis. In multivariate analysis of a larger group of 2658 cases of primary breast carcinomas (including the 1529 study cases) when histological grade, lymph node status and tumour size were entered, grade was the most important factor in predicting for survival. When histological type of carcinoma was included it was also found to be independently significant, although comparatively of less importance than grade. We conclude that tumours should be typed and graded in order to predict prognosis most accurately and to enable the choice of optimum treatment for women with primary breast carcinoma.     

Spindle cell carcinoma of the breast: A clinocopathologic and ultrastructural study

The clinical and pathologic features in six cases of spindle cell carcinoma of the breast were reviewed. Histologically this tumor is characterized by sheets of spindle cells often containing squamous epithelial islands and numerous cystic spaces lined by epidermoid carcinoma or benign appearing squamous epithelium. Areas of transition from the squamous epithelium or epidermoid carcinoma to malignant spindle cells were seen in all cases. Features of squamous epithelial differentiation were found in the spindle areas of the one tumor examined by electron microscopy. The prognosis in this neoplasm is similar to that in the more common breast carcinomas. Spindle cell carcinoma therefore should be distinguished from broader category of “metaplastic carcinoma”, since this term includes a heterogeneous group of tumors of uncertain histogenesis and prognosis.     

Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney.

The classification of urothelial neoplasms of the kidney traditionally has been similar to that of urinary bladder tumors. Several years ago, the classification of papillary urothelial neoplasms was revised. The current study focuses on the application of the 1998 World Health Organization (WHO)/International Society of Urological Pathology classification system to 102 renal pelvic urothelial neoplasms and compares it to the 1973 WHO classification scheme. In this study, all tumors were classified as urothelial carcinomas, and the majority (85%) were papillary. Most patients with papillary tumors presented with 'superficial' disease (< or = pT1). With the 1998 system, most papillary carcinomas were high grade, and were more often invasive as compared to low-grade tumors. Only 34% were low-grade papillary tumors and, of these, most (93%) were noninvasive. With the 1973 system, most papillary tumors were grade 2 or 3, with invasion more common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous group; with 1998 criteria, nearly one-half were high grade and the other half low grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998 grading methods was associated with stage (P=0.001). Our study reveals that papillomas and papillary urothelial neoplasms of low malignant potential are uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are most often carcinomas and are more commonly high grade than low grade. Although both the 1973 and 1998 systems showed a significant association with tumor stage, grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998 system provides useful information in that it more clearly defines a papillary tumor's grade and selects for a group of tumors, namely low-grade papillary urothelial carcinomas, for which a low likelihood of invasion can be predicted.     

Sweat gland carcinomas with nodular and basaloid differentiation

Sweat gland carcinomas pose a significant diagnostic challenge to histopathologists due to their rarity, their considerable morphological spectrum and their frequent resemblance to cutaneous metastases of visceral primaries. The behavior of sweat gland carcinomas ranges from indolent to aggressive with significant metastatic potential and mortality rates. Confident and correct diagnosis is therefore crucial to guide treatment and predict outcome. This review focuses on four sweat gland carcinomas, cutaneous cribriform carcinoma, endocrine mucin-producing sweat gland carcinoma, spiradenocarcinoma and aggressive digital papillary adenocarcinoma. These tumors show many overlapping histological features and are characterized by a lobular architecture and basaloid differentiation but vastly different clinical behavior. The article emphasizes subtle differentiating features, clinical and morphological clues and immunohistochemical expression patterns, and the key differential diagnoses are provided for each entity.